The long term goal of our studies is to understand the processing of complex sounds such as speech by the auditory nervous system in enough detail to construct mathematical models that summarize the essential features of that processing. This understanding is fundamental to the rational design of auditory prostheses, including cochlear and central nervous system (CNS) implants and hearing aids and to the design of diagnostic, treatment and rehabilitation paradigms for disorders of auditory perception in human patients. In this project we focus our attention on the role of inhibitory interactions in the signal processing carried out by the cochlear nucleus (CN). The input to the CN is from the auditory nerve (AN). The CN is the first stage of CNS processing of the neural code for sound which is produced in the cochlea. Project 2 explores the anatomical connections to and within the CN that form the structural basis for signal processing while Project 3 measures the membrane properties of CN cells responsible for their signal processing capacities. In this project we combine the results of Projects 2 and 3 to construct a model that summarizes the CN input/output relationships for complex stimuli as measured in this and other laboratories. Recent results from our laboratory have suggested that inhibitory interactions in the CN play a direct role in sharpening the neural representation of complex spectra in the CN relative to that in the AN. We are particularly interested in chopper units in the anteroventral CN (AVCN) which provide a particularly robust representation of complex spectra. The first aim of the project is to develop a quantitative physiological measure of strength of inhibitory inputs that can be used to compare inhibition across different populations of CN units. We have shown that inhibition can change the temporal patters of firing of these units and we will measure these changes quantitatively in the chopper population. These data will provide strong constraints on models of chopper units and will serve to hasten the development of neural models. We will use pharmacological tools to enhance or block inhibition in the CN in order to help illuminate the mechanisms of CN inhibition. To test and refine our neural models, we will measure responses of AVCN choppers in two complex stimulus situations where inhibition is likely to play an important role: speech in noise and narrowband amplitude modulation at high sound levels. We expect to find a correlation between strength of inhibition to a population of cells and the quality of neural representation in these stimulus situations.